U.S. patent number 5,635,072 [Application Number 08/381,380] was granted by the patent office on 1997-06-03 for simulated moving bed adsorptive separation process.
This patent grant is currently assigned to UOP. Invention is credited to Michael G. Moran.
United States Patent |
5,635,072 |
Moran |
June 3, 1997 |
Simulated moving bed adsorptive separation process
Abstract
Various chemicals such as pharmaceuticals and petrochemicals are
chromatographically separated in small quantities using an
apparatus comprising a number of serially connected
adsorbent-containing chambers. The chambers are linked together
with valving necessary to simulate the continuous countercurrent
flow of the adsorbent and liquid phases. The apparatus employs
three three-port valves per chamber to direct liquid flow. Pressure
pairing of the valves and the four major process streams protects
product purity.
Inventors: |
Moran; Michael G. (Crystal
Lake, IL) |
Assignee: |
UOP (Des Plaines, IL)
|
Family
ID: |
23504813 |
Appl.
No.: |
08/381,380 |
Filed: |
January 31, 1995 |
Current U.S.
Class: |
210/659;
210/677 |
Current CPC
Class: |
B01D
15/1842 (20130101); B01D 2215/023 (20130101) |
Current International
Class: |
B01D
15/18 (20060101); B01D 15/10 (20060101); B01D
015/08 () |
Field of
Search: |
;210/656,662,670,677,96.1,198.2,253,264,269,659,672 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Other References
Armand J. deRosset et al. "Liquid Column Chromatography as a
Predictive Tool for Continuous Countercurrent Adsorptive
Separations." Ind. Eng. Chem. Process Des. Dev., vol. 15, No. 2,
1976, pp. 261-266. .
Giuseppe Storti et al. "Performance of a Six-Port Simulated
Moving-Bed Pilot Plant for Vapor-Phase Adsorption Separations."
Separation Science and Technology, 27 (14), 1992, pp. 1889-1916.
.
Ching et al. "Preparative resolution of praziquantel enantiomers by
simulated counter-current chromatography". Journal of
Chromatography, 634 (1993) pp. 215-219. .
Negawa et al. "Optical resolution by simulated moving-bed
adsorption technology." Journal of Chromatography, 590 (1992), pp.
113-117..
|
Primary Examiner: Cintins; Ivars
Attorney, Agent or Firm: McBride; Thomas K. Spears, Jr.;
John F.
Claims
What is claimed:
1. In a liquid-phase simulated moving bed process for the
separation of two components of a feed stream using an apparatus
comprising a plurality of adsorbent chambers and at least a first
and a second multiport valve per adsorbent chamber, the improvement
which comprises alternately controlling the flow of a separate
process input stream and a separate process output stream through
each of the multiport valves and maintaining the input and output
streams of each multiport valve at a different pressure, with the
pressure of the input stream of the first multiport valve being
higher than the pressure of the output stream of the first
multiport valve and with the pressure of the output stream of the
second multiport valve being higher than the pressure of the input
stream of the second multiport valve, and with the input stream of
the first multiport valve being rich in a mobile phase and being
the highest pressure stream employed in the process.
2. A simulated moving bed process for separating a multicomponent
feed stream by liquid chromatography in a plurality of serially
interconnected adsorbent chambers, which process comprises the
steps of:
(a) passing the feed stream, which comprises an extract component
and a raffinate component, through a first header conduit and into
a first multiport valve and then through a first transfer conduit
and into the inlet of a first adsorbent chamber, with the first
adsorbent chamber containing a bed of adsorbent which is capable of
selectively adsorbing the extract component;
(b) simultaneously passing an internal process stream removed from
the outlet of a second adsorbent chamber, located immediately
upstream of the first adsorbent chamber, through a second multiport
valve and into the inlet of the first adsorbent chamber while
removing a first process stream from the outlet of the first
adsorbent chamber and passing the first process stream through a
third multiport valve and into the inlet of a third adsorbent
chamber, which is located immediately downstream of the first
adsorbent chamber;
(c) indexing the positions of valves present in the apparatus such
that the feed stream is passed into an adsorbent chamber located
downstream of the first adsorbent chamber;
(d) withdrawing an extract stream comprising the extract component
from the outlet of the second adsorbent chamber, passing the
extract stream through the second multiport valve and then dividing
the extract stream into a first portion, which is passed into the
first adsorbent chamber as said internal process stream, and a
second portion which is passed first into the first multiport valve
and then into a second header conduit and removed from the process
as an extract product stream;
(e) indexing the positions of valves present in the apparatus such
that the extract stream is withdrawn from an adsorbent chamber
located downstream of the first adsorbent chamber;
(f) passing a mobile phase stream comprising a desorbent compound
through a third header conduit and a fourth multiport valve and
into the first adsorbent chamber, with the effluent of the first
adsorbent chamber being passed into the third adsorbent chamber
through the third multiport valve;
(g) indexing the positions of valves used in the apparatus such
that the mobile phase stream is passed into an adsorbent chamber
located downstream of the first adsorbent chamber; and,
(h) withdrawing a raffinate stream from the outlet of the second
adsorbent chamber and passing the raffinate stream through the
second and fourth multiport valves and into a fourth header
conduit, and withdrawing the raffinate stream from the process.
3. The process of claim 2 further characterized in that the feed
stream has a pressure above 500 psi.
4. The process of claim 2 wherein the mobile phase stream has a
pressure higher than the extract stream, which has a higher
pressure than either the feed stream or the raffinate stream.
5. The process of claim 2 wherein an aliquot portion of the
raffinate stream being withdrawn from the second adsorbent chamber
is diverted into the inlet of the first adsorbent chamber and a
solvent stream comprising high purity desorbent compound is
recovered from the outlet of the first adsorbent chamber.
Description
FIELD OF THE INVENTION
The invention relates to chromatographic apparatus for use in the
small scale separation of chemicals such as chiral pharmaceuticals.
The invention more specifically relates to a novel apparatus and
novel method of operation of a continuous adsorptive separation
process in which the movement of the adsorbent is simulated. In a
limited embodiment the invention relates to the construction and
operation of small scale simulated moving bed adsorptive separation
pilot plants for use in the pharmaceutical and fine chemical
industries.
RELATED ART
U.S. Pat. No. 3,706,812 issued to A. J. De Rosset and R. W. Neuzil
describes a pilot plant scale simulated moving bed adsorptive
separation process unit. This reference also describes an
operational problem of such units when they are built in the manner
of larger units and include a "pump around" pump used to maintain
liquid circulation in the process. The invention described in this
reference is the utilization of a check valve at outlet end of each
adsorbent bed to maintain unidirectional flow.
In an article appearing at page 261 of Industrial and Engineering
Chemistry, Process Design and Development, Vol. 15, No. 2 (1976), a
further description of this type of pilot plant is provided. This
article also gives examples of the usage of the system and the
chemical component profiles which are generated in the plant.
In an article appearing at pages 1889-1916 of Separation Science
and Technology, Vol 27, No. 14, (1992), there is illustrated the
construction of a six- and twelve-bed simulated moving bed pilot
plant using a number of multiport valves instead of a single rotary
valve. One valve is used for each of the inlet and outlet streams,
including a desorbent effluent stream.
U.S. Pat. No. 4,434,051 issued to M. W. Golem describes an
apparatus for performing a simulated moving bed adsorptive
separation which employs a large number of multiport valves instead
of a rotary valve as used in large scale simulated moving bed
process units.
In an article published at pages 215-219 of the Journal of
Chromatography, 634 (1993), there is shown a valve arrangement for
use on a simulated moving bed adsorptive separation pilot
plant.
The separation of racemic or chiral material by continuous
simulated moving bed adsorptive separation was described in a
presentation conducted at PREP '91 in Arlington, Va., U.S.A. on May
13-15, 1991 and printed in the Journal of Chromatography, 590
(1992) pages 113-117. The article gives a diagram of a small scale
system with eight adsorbent chambers and four rotary valves.
U.S. Pat. No. 3,268,605 illustrates a control system which may be
used on simulated moving bed process units, with the flow rate of
three of the main process streams being set by flow controllers and
the flow of the last stream being set by a pressure control valve.
A similar control philosophy as applied to a simulated moving bed
system for chiral separations is shown in patent application WO
92/16274 assigned to Bayer Aktiengesellschraft. This reference,
however, employs a number of dual position valves to simulate the
use of a moving bed of adsorbent.
BRIEF SUMMARY OF THE INVENTION
The invention is a method of operating a simulated moving bed
adsorptive separation process which eliminates the need for a "pump
around" system used to circulate fluids in the overall process. The
subject invention also has a number of benefits compared to the
prior art when applied to pharmaceutical separations or other
separations requiring a high degree of product purity. The subject
invention utilizes a valving system which blocks the flow of liquid
through the process immediately upstream of the bed adsorbent
chamber receiving the desorbent stream. In one limited embodiment
of the invention, the desorbent material contained in the next bed
upstream of the point of desorbent injection is discharged from the
bed at a controlled rate and at least partially recycled as
desorbent.
One broad embodiment of the invention may be characterized as an
apparatus for performing a continuous chromatographic separation
which comprises a plurality of adsorbent chambers, with each
chamber having an inlet and an outlet and having a pair of
multiport valves associated with the chamber, with the inlet of
each chamber being in fluid communication with a first port of a
first multiport valve of the pair via a first conduit means and
also being in fluid communication with a first port of a second
multiport valve of the pair via a second conduit means; and with
the first multiport valve of each pair being in fluid communication
with a first header conduit via a second port and a third conduit
and also in fluid communication with a second header conduit via a
third port and a fourth conduit and the second multiport valve of
each pair being in communication with a third header conduit via a
second port and fifth conduit and a fourth header conduit via a
third port and a sixth conduit; and with the outlet of each chamber
being in fluid communication with the first port of said first
multiport valve via first and second ports of a third multiport
valve associated with each chamber and a seventh conduit means and
in fluid communication with the first port of said second multiport
valve via the first and second ports of the third multiport valve
and an eighth conduit means, and with a third port of the third
multiport valve being in communication with a recycle conduit
header via a ninth conduit means.
BRIEF DESCRIPTION OF THE DRAWING
The Drawing is a simplified diagram of a pilot plant scale
apparatus built according to the subject invention for the
adsorptive separation of hydrocarbons through the use of simulated
countercurrent liquid-adsorbent flow in the seven adsorbent
chambers A-G.
DETAILED DESCRIPTION AND PREFERRED EMBODIMENTS
Simulated moving bed adsorptive separation is used in a number of
industries to perform useful separations of a variety of chemicals
including petrochemical intermediates. It is used in the recovery
of para xylene for the production of polyesters and in the recovery
of normal paraffins in the production of linear olefins which are
then consumed as detergents precursors. Adsorptive separation is
also being investigated as a tool in many new separations of a wide
variety of chemicals including chiral compounds and intermediates
used in the production of experimental and therapeutic drugs. These
efforts are normally conducted in small scale pilot plants which do
not require much feed stock, adsorbent or plant space. This is
especially true when the materials which are to be separated are
expensive due to their rarity or complicated production
techniques.
Pilot plant scale simulated moving bed adsorptive separation units
have been troubled by components mixing in the connecting line
volumes associated with the use of a pump referred to in the art as
a "pump around" pump. One of the primary problems is that the
mixing inherent in the pump and this line volume destroys the sharp
component concentration profiles which the adsorbent creates and
which is necessary to perform the desired separation. This problem
is more troublesome to pilot plant scale equipment since the
inventory of process liquid in the connecting lines and in the pump
becomes a larger fraction of the total volume of the adsorption
apparatus as the size of the plant decreases. It is an objective of
this invention to provide a small scale pilot plant system for
which does not require a pump-around loop and pump.
This problem is discussed in some detail and a solution utilizing
check valves at the inlet of each adsorbent bed is presented in
previously cited U.S. Pat. No. 3,706,812. This solution, however,
was aimed at relatively low pressure units. When a pilot plant
employs a small particle size adsorbent, that is one less than 50
microns in average diameter, then the pressure drop and operating
pressure in the unit increases substantially. Whereas the pressure
drop (desorbent inlet to raffinate outlet) may be in the order of
20-30 psi in a large scale pilot plant, the pressure drop in a
pilot plant using high pressure liquid chromatography (HPLC)
techniques may be up 1,500 psi or more. This high pressure
differential makes utilization of the solution presented in the
just cited reference impractical. It is therefore a specific
objective of the subject invention to provide a high pressure pilot
plant scale simulated moving bed adsorptive separation process
which does not require check valves.
Working at the pressures involved with high pressure liquid
chromatography raises other practical problems. For instance, the
mechanical problems involved with preventing leaks in rotary valves
increases greatly with an increased pressure. The valves tend to be
of a specialty nature which increases the cost of the valves and
the entire apparatus. It is a further objective to provide a small
scale high pressure apparatus for simulated moving bed
chromatography which employs valves having three or less ports per
valve.
As previously mentioned there is presently much interest in the
separation of chiral compounds for use in pharmaceuticals. The
pharmaceutical industry requires very high levels of purity and
therefore cannot tolerate backmixing of feed and product components
in the mechanical arrangement used for simulating moving bed
chromatographic separations. Specifically, transfer lines should
not commingle streams by transporting both the feed and the
effluent streams and valve leakage must be minimized compared to
common petrochemical separations. It is a primary objective of the
invention to provide an apparatus for performing simulated moving
bed separations which must produce very high-purity products.
Both the stationary phase and the desorbent or mobile phase used to
separate chiral compounds can be very expensive. It is a further
objective of the invention to provide an adsorptive separation
process which requires a reduced amount of desorbent material.
The subject invention achieves these objectives by the use of a
unique flow scheme that utilizes a number of three way valves and a
novel conduit arrangement to simulate the continuous countercurrent
flow of the adsorbent and process streams. In the simulated moving
bed technique, the normal chromatographic profiles which develop as
a multicomponent feed mixture passes through a lengthy bed of
adsorbent is in effect frozen in place by the periodic advancement
in the location of the addition and withdrawal points of the feed,
desorbent, extract and raffinate streams. A shift of the feed and
withdrawal points in the direction of fluid flow simulates movement
of solids in the opposite direction. Liquid flows in a downstream
direction in the apparatus of the invention, which gives a
reference for the following description.
As used herein several terms have specific meanings. The term
"rich" is intended to indicate a concentration of the indicated
compound or class of compounds greater than 50 mole percent. The
term "multiport valve" is intended to refer to a valve which has
ports for connecting a single primary process stream transfer line
to two or three secondary process stream transfer lines and for
allowing selective flow between any one of the secondary transfer
lines with the primary transfer line. A three-way ball valve is an
example of a multiport valve. The term "header" is used to indicate
one of the four primary transfer lines used to pass a primary
process stream into the overall process or to remove a primary
process stream from the overall process, and which is in
communication via one set of multiport valves with all of the
adsorbent chambers used in the process. The primary process streams
are the feed stream, desorbent stream, raffinate stream and extract
stream.
The overall process flow of the subject invention can be best
described by reference to the Drawing. The Drawing is a simplified
flow diagram of an embodiment of the invention employing seven
adsorbent beds or chambers labeled A through G. Seven chambers are
shown on the drawing basically for ease of presentation and
description. The number of adsorbent chambers may vary to suit the
situation. Most systems will have eight or more chambers, with
twenty-four being about the maximum practical number of
chambers.
The zone numbers used in this description of a simulated moving bed
process are those which have become established in the art, and
which are used and illustrated in U.S. Pat. Nos. 2,985,589;
3,310,486; 3,392,113 and 4,475,954 which are incorporated herein by
reference for their description of the operation of these processes
and equipment for its performance. The distribution of the chambers
in any one zone of the apparatus depends on such factors as
adsorbent performance, desorbent strength, etc.
The beds are serially interconnected through the various conduits
and valves in a manner described in more detail below. As an
overview of the process, it may be noted that at the point in time
depicted in the Drawing, the feedstream of header line 1 is
entering adsorbent chamber B through line 75 and will cause a
displacement of the liquid in the bed, which will flow out of the
bottom end of the chamber through line 54. Beds A and B form Zone
I, the adsorption zone. Different fluids flow simultaneously
through the zones maintained in the serially interconnected
adsorbent beds. While the feed is flowing through the chambers of
zone I, a stream of desorbent from header line 2 is simultaneously
withdrawn from a desorbent storage tank not shown and passed
through lines 40 and 79 to chamber F. This in turn displaces liquid
out of the bottom of bed F which flows through line 58 to valve 25,
and is directed to the top of adsorbent bed E via lines 64, 99 and
78. Beds F and E form the desorption zone, zone III. Extract liquid
travels from chamber E to line 3 via lines 63, 91 and 49. Beds C
and D form zone II, the purification zone and bed G is used as the
buffer zone, zone IV.
While the drawing illustrates the chambers as being laid out next
to one another in a row, it is preferred that the chambers are
arranged in a pattern such as a circle or rectangle which results
in the volume in the conduits between each of the sequential beds
being substantially equal.
The separation which occurs while the feed stream passes through
the adsorbent retained in chambers B and A results in the formation
of a raffinate stream having a higher concentration, relative to
the feed stream, of one or more component(s) originally present in
the feed stream. This component will be the component which is less
strongly held by the adsorbent. Often, but not necessarily, the
most strongly adsorbed component is the desired product. Adsorption
of this component forms the raffinate stream comprising the less
strongly held component(s) and admixed desorbent material which is
withdrawn from the bottom of adsorbent chamber A through line 53
and delivered to valve 20. Valve 20 directs the flow of the
desorbent material into line 73 through which it flows to lines
101, 87 and 46. A back-pressure valve or regulator 103 is
preferably used as the device which regulates the flow rate of the
raffinate stream out of the process via the raffinate header line
4. Note that the raffinate flow rate is not really set by this
valve. The valve's primary function is to maintain a constant
pressure at this point in the system. The flow rate is actually set
by the flow rates of the three other streams.
The following is a more detailed description of the layout of the
apparatus and the flows through the apparatus at one particular
point in time. When the apparatus is being used to simulate a
countercurrent movement of the adsorbent versus the liquid, valves
will be opened or closed by a computerized control system which
periodically advances the inlet points to each zone one chamber. To
simulate countercurrent flow this advancement is to the left. The
flow of the four basic streams of the process will therefore move
through different lines and valves at different points in time.
Eventually each stream flows through each adsorbent chamber in a
repeated cycle. At the time being depicted in this description, a
feedstream entering through line 1 flows to the right to the
intersection with line 30. Because of open valves which allow fluid
flow, the feedstream flows into line 30 and through valve 9. Valve
9 directs the feedstream into line 89 which transfers the
feedstream into line 96 from which it flows through line 75 into
adsorbent chamber B.
The structure of the apparatus comprises a number of valves and
connecting lines set by the number of chambers which it is desired
to employ. These lines and valves are arranged in a symmetrical
pattern which may be discerned by reference to the drawing. For
each chamber there is transfer line descending from the feed header
line 1 with these lines being labeled 29 through 34 on the drawing.
Each of these lines leads to an associated multiport valve with the
valves receiving the feedstream being valves 7, 9, 11, 13, 15, 17
and 19. Each of these valves in turn has a port by which it
connects with a line leading to an associated adsorbent chamber. In
the drawing these lines are lines 88 through 94. Each of these
lines in turn connects with a transfer line labeled 95 through 101
which finally connects with the single transfer line leading to the
top of each adsorbent chamber. These lines are labeled 74 through
80 on the drawing. This sequence of lines forms the route traveled
by the feedstream into the rightmost adsorbent chamber in zone I,
the adsorption zone. In the next step in the advancement of the
inlet ports, the feed stream would flow from header line 1 into
line 29, through associated valve 7 into line 88 and finally
through lines 95 and 74 into chamber A.
It is important to note that the flow of liquid through the various
lines is determined by the position of the valve(s) which is/are
open. A great majority of the valves depicted in the drawing as
being located near the inlet or upper end of the chambers are in a
totally closed position at any time. In contrast, the valves
depicted in the drawing as being associated with the outlets of the
chambers; that is, valves 20 through 26 are normally in an open
position except for one valve when an optional "recycle" stream is
not being recovered. This, and a variation, are described below in
more detail.
Of the 14 valves depicted as being associated with the upper end of
the adsorbent chambers, only 4 valves are positioned at any one
time to allow fluid flow through the valve. These are the valves
through which the feed and desorbent pass into the chambers and the
extract and raffinate are removed from the chambers. All of the
other valves are in a totally closed position.
The flow of the feedstream into the upper end of chamber B through
line 75 displaces the liquid in the chamber, which flows downward
through line 54 and is diverted into line 60 by valve 21. The
liquid continues through lines 95 and 74 due to valves 6 and 7
being in a closed position. The liquid then flows into the top of
chamber A. Valve 20 is positioned to direct the flow of the
displaced material of line 53, which is the nonadsorbed or
raffinate material into line 73 which carries it to the
intersection with line 101. Because valve 19 is totally closed and
valve 18 is positioned with an appropriate open port, the raffinate
material flows into line 87 through valve 18 and into valve 46
which delivers the raffinate to the raffinate header line 4.
At the same time that the feed is flowing into the apparatus
through line 1, a desorbent stream flows into the apparatus through
the header line 2. In a manner which mirrors the delivery of the
feedstream, the desorbent header 2 is connected to the inlet of
each adsorbent chamber through a series of transfer lines and one
multiport valve associated with the inlet of each adsorbent
chamber. For instance, for bed A the desorbent would travel through
line 35, valve 6 and lines 81 and 74 to enter adsorbent chamber A.
However, at the time being depicted in this description of the
drawing the desorbent is allowed to flow through line 40 by the
open port of valve 16 and continues to flow through lines 86 and 79
into the inlet end of the adsorbent chamber F. Liquid displaced
from the adsorbent chamber F flows through line 58 and valve 25
into line 64. Line 64, like the other lines 60 through 65, is
employed to connect the outlet of each chamber to the sequential
adsorbent chamber located immediately downstream. The liquid stream
leaving chamber F is thereby passed through lines 64, 99 and 78
into the inlet of adsorbent chamber E. Chambers F and E form Zone
III, the desorption zone. The liquid displaced from the adsorbent
chamber E forms the extract stream and is removed through line 57
for passage into valve 24. The position of valve 24 directs this
extract stream into line 63 with the open position of valve 13
allowing the fluid to pass through line 91 into line 49 which
connects to the extract header 3. The extract header 3, in a manner
similar to the other header lines, is connected to the upper end of
each adsorbent chamber by lines 47 through 52. The extract stream
flows at some time in the process cycle through each of lines 88
through 94 and valves 7, 9, 11, 13, 15, 17 and 19.
The rate of withdrawal of the extract stream is set by a flow rate
control valve 102. The outlet rate of the raffinate stream is set
by a pressure control valve 103. The flow rate control valve
regulates the effluent rate of the extract stream of header line 3
to be less than the feed rate of the desorbent stream of header
line 2.
A portion of the extract material flowing through line 63 equal to
the difference between the desorbent and raffinate stream flow
rates is allowed to pass into line 98. This material is charged to
the inlet of the purification zone (zone II) and is referred to in
the art as zone II material. The function of the liquid flowing
through this zone is remove raffinate material from the
nonselective pore volume of the adsorbent and chambers of the
purification zone. This material flows through lines 98 and 77 into
the inlet of the adsorbent chamber D. The liquid displaced from the
adsorbent chamber D flows through line 56 into valve 23 which
directs it into line 62. The liquid then continues through lines 97
and 76 into the inlet end of the adsorbent chamber C. The liquid
displaced from the adsorbent chamber C flows through line 55 and
valve 22 into line 61. At this point, it joins the feed material
from line 89 and flows into the adsorption zone (zone I). The
raffinate material flushed from the purification zone therefore
flows into the adsorption zone. The raffinate components in the
material being flushed into the adsorption zone in this manner
merely travel through the adsorption zone and do not interfere with
the adsorption of the desired component from the feedstream.
The flow rates of the feed stream, desorbent stream and extract
stream are all regulated on the basis of flow rate, which is
preferably held constant. Only the raffinate stream rate is on
pressure control.
At the other end of the sequence, a portion of the raffinate stream
of line 101 may be allowed to flow into line 80 and the upper end
of adsorbent chamber G in order to displace the liquid present in
the adsorbent chamber G. In the time period now being described,
adsorbent chamber G is the adsorbent chamber which had received the
desorbent material in the previous step. At the end of that step,
the chamber liquid is comprised of essentially 100% desorbent
material. This optional displacement step performed by feeding
raffinate material into the top of the adsorbent chamber G, also
referred to herein as the "dead bed" is to allow the recovery of
this desorbent material as the recycle stream. The displaced
desorbent exits the bottom or outlet of adsorbent chamber G through
line 59 and is directed by the multiport valve 26 into line 72. The
displaced fluid is allowed to flow to the right through lines 72
and 5 into optional valve 28.
At this point in time valve 26 is positioned to allow flow into
line 5 and all of the other valves associated with the outlet of
the chambers; e.g., valves 20, 22, and 25 are positioned to have
fluid flow to the left to the next chamber. Valve 28 may be
employed in conjunction with an optional on-line analytical device
not shown to recover high purity desorbent. Normally the flow of
the raffinate material through the dead bed would be controlled at
a set rate and for a set time which will result in an optimum
recovery of high purity desorbent. However, the analytical
instrument could monitor the composition of the material flowing to
the right in line 5 and entering valve 28. The high purity
desorbent is collected in line 27 and may be recycled to line 2.
Material which is contaminated; that is, a mixture of desorbent and
raffinate, is diverted into line 66 by the operation of valve 28 in
response to the analytical device. Line 66 would normally connect
to the raffinate header or other raffination collection system.
This flushing of the dead bed allows the recovery of valuable
desorbent material. It has no detrimental effect on the separatory
performance of the process as it merely results in the adsorbent
chamber G being loaded with a mixture of desorbent and raffinate
components. In the next step in the process adsorbent chamber G
becomes the second bed in zone I, the adsorption zone. The
adsorbent, which is now free of desorbent material, can still
function in the normal manner, and the contents of the chamber
flows into the raffinate stream.
The drawing illustrates several advantages of the subject
invention. First of all, the apparatus does not employ a pumparound
stream as utilized in the original simulated countercurrent process
technology. This simplifies the process, reduces the amount of line
volume in the apparatus, and results in a generally improved
apparatus. A subtle feature of the invention is that the
arrangement of valves and lines greatly reduces or eliminates
contamination problems which can result from the failure of seals
in the valves. This benefit is achieved by means of the valving
arrangement and the cascading operating pressures used in the
process. For instance, the extract stream has a higher pressure
than the feed stream. Therefore, if there is a leakage in valve 9,
which is the active valve for directing the feed stream at the
point in time depicted in the above description, the leakage will
be of extract material into the transfer conduit 89. Any leakage by
a valve which directs the flow of the extract stream is therefore
into a conduit which passes the leaked material into the feed
stream. In essence the leakage merely recycles the extract.
Similarly, any leakage of desorbent materials through the seven
valves which direct the flow of this material is into the raffinate
stream of line 4. This merely dilutes the raffinate stream.
This means to produce a high-purity product is referred to herein
as the proper "pressure-pairing" of the two main process streams
which flow through each of the two multiport valves; e.g., 6 and 7,
associated with the inlet of each chamber. By pressure pairing it
is meant that the header line streams are held at different
pressures and then paired together at the valves such that any
leakage does not cause harmful contamination of the desired
product. In the present case the four streams are maintained at
different pressures with the mobile phase (desorbent) always being
at the highest pressure. The extract stream has the next highest
pressure. This ensures that the extract purity will always be free
of contamination by a raffinate component. While the pairing of the
streams on the valves should by itself prevent some admixture
possibilities, such as mobile phase and extract, the pressure
cascade will have the same effect. For instance, any leakage of
mobile phase into the extract would merely dilute the extract, and
any leakage between the extract and the remaining two streams must
be in the form of extract flowing into the feed or raffinate. While
this can reduce the extract recovery rate, it will not reduce the
purity of the extract product. It is also desired to have the feed
pressure greater than the raffinate stream pressure. The preferred
order of pressures is therefore mobile
phase>extract>feed>raffinate. These same advantages are
obtainable when the raffinate is the intended product.
Admittedly some of the pressure cascade sequence is set by the
process itself. For instance, the pressure of the mobile phase must
be greater than the extract since the mobile phase pushes the
extract out of the system. Likewise the feed stream inlet pressure
must be greater than the raffinate outlet pressure as the feed
pushes the raffinate through the system.
The second element of the preferred pressure pairing arrangement
matches one feed and one effluent stream to each of the two
multiport valves which handle input and output from each adsorbent
chamber. The invention therefore provides an improved valving
arrangement for an apparatus for performing a simulated moving bed
separation of the components of a feed stream at a pressure greater
than 500 psi which may be characterized as a multichamber apparatus
for performing a liquid-phase simulated moving bed separation of
two components of a feed stream with the apparatus comprising at
least two valves per adsorbent chamber; characterized by the
improvement which comprises using at least a first and a second
multiport valve per adsorbent chamber, with each of the first and
the second multiport valves directing the flow of a separate
process input stream and a separate process output stream, and
maintaining the input and output streams of each multiport valve at
a different pressure, with the input stream of the first multiport
valve being higher than the pressure of the output stream and with
the pressure of the output stream of the second multiport valve
being higher than the pressure of the input stream of the second
multiport valve, and with the input stream of the first multiport
valve being rich in a mobile phase and being the highest pressure
employed in the apparatus.
The subject invention leads to higher purity products in several
different ways. In addition to this "pressure pairing", the
physical layout of the apparatus minimizes the unflushed conduit
and fitting volume which carry both the intended product and a
stream containing compounds which would be a contaminant in the
product. The most troubling lines which remain in the apparatus are
the relatively short ones (numbers 81-94) which connect the
multiport valves to the conduit system which connects the outlet of
one chamber to the inlet of the next chamber. The invention allows
these lines to be very short and exposed to fluid flow which will
tend to help flush them.
While this description of the figures was presented on the basis of
all the flows through the adsorbent beds being in a downward
direction, there is no inherent requirement for this to be so. The
flow through the adsorbent beds may be in an upward direction or in
a combination of upward and downward directions in different
beds.
As previously stated, there is preferably no direct control on the
rate of flow of the raffinate stream. The flow rate of this stream
is set by the rate of flow of the two streams into the process,
namely, the feed and desorbent streams and the controlled rate of
flow of the extract stream which leaves the process.
All but one of the valves 20-26 associated with the outlet of the
chambers normally have their ports open to fluid flow at all times
during the use of the apparatus. One valve is in a position which
prevents flow through its ports to the next bed. The location of
this one blocked port is stepped through the adsorbent beds,
coordinated with the stepping of the other valves, in a manner
which maintains unidirectional flow through the apparatus. This
flow control through the indexing of the valves eliminates the need
for the check valve in a line associated with each chamber A-G to
provide unidirectional flow. This is another advantage to the
subject apparatus, especially when applied to high purity
separations such as pharmaceuticals.
In a variation of this, one valve is positioned differently in
order to divert flow of a stream comprising recoverable desorbent
out of the system. This optional stream is referred to herein as
the desorbent recycle or simply the recyle stream. It is the
material removed from the "dead bed" and is preferably only
withdrawn at a combination of time and rate which results in high
purity desorbent being remove. In this variation all of the valves
are open to some flow during the time the recycle stream is
withdrawn.
It must be noted that the previously described "dead bed"
nomenclature could be misleading when the optional desorbent
recycle stream is withdrawn for reuse or analysis. The withdrawal
of this stream, which has a reduced flow rate compared to the main
streams, does induce some flow through the otherwise stagnant dead
bed chamber. The withdrawal of this stream is optional. The desire
to recover this desorbent for reuse increases with the size and
length of operation of a specific apparatus. That is, as the total
recoverable volume of desorbent increases this line becomes more
desirable. Other factors relevant to the desirability of recovering
this desorbent recycle stream is the cost and difficulty of
recovering desorbent from the collected raffinate and extract. The
collected raffinate and extract will contain some desorbent and
failure to withdraw the desorbent via line 11 increases the amount
of desorbent in these streams.
The use of the dead bed and the recovery of mobile phase liquid
from this bed has the subtle benefit of making the zone I operation
more efficient. This is because the adsorption profiles which exist
in the system are allowed to move further downstream, with part of
the profile entering the dead bed. The effect is equivalent to
using a bigger zone I.
The Drawing is only intended to explain the invention by
illustrating one preferred embodiment. Many variations departing
from the apparatus depicted in the drawing are possible. For
instance, it will be readily recognized by those skilled in the art
that the flow of the main process or header streams, that is the
feed, desorbent, extract and raffinate streams, can be controlled
in a number of different ways. The use of pumps to set the rate of
three streams is but one example. Another example would be the use
of flow control valves on the two outlet streams or pressure
control valves on the inlet streams or some combination of these
valves. The depiction of the valves on the drawing should not be
viewed as controlling the type of valve which may be used. For
instance a multiport valve having a common feed port and four
outlet ports can be used as the valve. In this instance two of the
ports would always be closed. Valve selection is primarily a matter
of performance, availability and price versus design
specifications.
The feed and desorbent streams will normally be fed to the unit by
pumps from small tanks located close to the unit. The raffinate and
extract streams will normally be collected in similar tanks located
close to the unit. Both the raffinate and/or extract streams may be
sent to thin film evaporators, fractional distillation zones or
crystallizers to recover solvent and the intended product. The
stream containing the undesired compound may be sent to a
conversion zone such as an isomerization or racemization zone to
produce more of the desired product and then recycled as feed.
There are a number of factors which remain constant during use of
the invention such as a chosen mechanical configuration and the
sequence in which the streams flow to and from the chambers. This
sequence, in a downstream direction, is desorbent, extract, feed
and raffinate, which sets the preferred cascade of relative
pressures. The step time will normally remain constant during a run
but may be varied to adjust performance. The real variables are the
number of beds assigned to each zone; e.g., adsorption or
desorption, the step time and the flow rate of three of the process
streams. The flow rates of the feed, desorbent and raffinate
streams are preferably controlled and hence variable. The flow rate
of the raffinate may then vary but is really dependent on control
of the other three streams.
The adsorbent particles may be in the form of any shape and of any
size suitable for use in high pressure liquid chromatography. The
composition of the adsorbent is not a controlling factor in the
invention, which may employ any commercially available
adsorbent.
The subject apparatus can be constructed from commercially
available components. The adsorbent modules or chambers are
preferably standard HPLC tubes but may be much larger. All of the
chambers will contain the same adsorbent. The adsorbent chambers
may be purchased filled with the adsorbent or the adsorbent(s) may
be loaded separately. Examples of suitable adsorbent material
include the cross-linked organic resins, natural or synthetic
zeolites including zeolites X, Y, L, ZSM, Beta and omega,
silica-alumina, the various adsorptive aluminas, pillared and
mesoporous materials including pillared clays, and nonzeolitic
molecular sieves (NZMS), such as silica alumino-phosphates and
aluminophosphates, and chiral stationary phases. Chiral stationary
phases are described in U.S. Pat. Nos. 5,254,258 and 5,290,440.
The mobile phase or desorbent may be any compound or mixture of
compounds which is a liquid at the chosen operating conditions,
does not react with either the adsorbent or the compounds being
separated and is tolerable or totally separable from the intended
products. The desorbent may contain a chiral moiety. Depending on
the compounds being separated the desorbent may comprise water,
ethanol, methanol, benzene, toluene, a dialkylbenzene or a
halogenated hydrocarbon.
Suitable valves and actuators are available commercially. The
conduits and connectors may be of standard design for HPLC
instruments used for the desired separation in the relevant
industry.
Despite the fact that the subject apparatus utilizes a large number
of conduits, the apparatus is not significantly troubled by
backmixing or intermixing of streams of different composition
within the internal volume of the conduits. The basic reason for
this is that all of the conduit length leading from the valves to
the four header lines for the feed, desorbent, extract and
raffinate streams is dedicated to carrying just one of these
streams. Only the line from column to column; e.g., lines 61 or 65,
and the short connectors, e.g., lines 81, 88 and 82, need to be
minimized.
The valves can be mechanically linked such that they are all
indexed simultaneously by a single drive mechanism. However, it is
preferred that a separate electrical or air-powered actuator is
provided for each valve. This allows the relative position of the
feed and withdrawal points to be adjusted as desired to thereby
adjust the number of adsorbent chambers in the different zones,
e.g., adsorption used in the process. An electrical system which
provides a means to monitor valve position is preferred.
A preferred embodiment of the subject invention can accordingly be
characterized as an apparatus for performing a continuous high
pressure liquid chromatographic separation which comprises a
plurality of adsorbent chambers, with each chamber having an inlet
and an outlet and being adapted to retain a fixed bed of a solid
adsorbent, and with the adsorbent chambers being arranged and
linked together in a repeating sequence by a plurality of conduits;
a first set of multiport valves, with the valves in the first set
being equal in number to said adsorbent chambers and with a first
port of each multiport valve in the first set being connected via
means comprising at least one unique conduit to the inlet of an
associated adsorbent chamber; a first header line the supplying a
feed stream to a second port of each multiport valve of said first
set of multiport valves; a second header line removing, via means
comprising a second unique conduit, an extract stream from a third
port of each of multiport valve of said first set of valves; a
second set of multiport valves, with the multiport valves in the
second set being equal in number to said adsorbent chambers and
with a first port of each multiport valve in the second set being
connected via at least one unique conduit to the inlet of an
associated adsorbent chamber; a third header line supply a
desorbent stream to a second port of each multiport valve of said
second set of multiport valves; a fourth header line removing, via
means comprising at least one unique conduit, a raffinate stream
from a third port of each of multiport valve of said second set of
valves; a recycle stream header line collecting desorbent material
from the outlet of said adsorbent chambers; a third set of
multiport valves, with the multiport valves in the third set being
equal in number to said adsorbent chambers and with; (i) a first
port of each multiport valve in the third set being connected via a
unique conduit to the outlet of an associated adsorbent chamber,
(ii) a second port of each multiport valve in the third set being
connected via a unique conduit to the inlet of the next sequential
adsorbent chamber and to the inlets of a multiport valve of the
first and the second sets of multiport valves and (iii) a third
port of each multiport valve in the third set being connected to
said recycle stream header line. By continuous process it is meant
that the feed stream and a desorbent stream are passed into the
apparatus at a uniform rate.
Operating conditions suitable for the subject process include a
temperature of about -50 to 300 degrees C., preferably 20 to 100
degrees C. It is generally preferred that the process is operated
with a positive pressure in the general range of about 700 to 25000
kPa. Representative flow rates for a small (exploratory separation)
scale unit are 0.1-2.0 ml/min for the feed and 2-20 ml/min for the
desorbent. Such units would employ conduits having internal
diameters of about 0.3 to about 0.6 cm and could produce up to
about 1.0 ton/year of dry product. Larger units would have quite a
bit larger flow rates, with the maximum feed flow rate being
limited only by equipment and economic considerations. The total
amount of dry product recovered from the extract in larger units
could reach 1000 kg/day.
While the subject invention is envisioned as being primarily
suitable for liquid phase flow, it is believed the operating
principles and apparatus could be applied to vapor phase flow.
As previously mentioned chromatographic separations can be applied
to a wide range of chemical compounds. Rather unusual chemicals
such as chiral pharmaceutical intermediates are just one example.
Fermentation broths are another. Nonchiral alkyl aromatics,
halogenated aromatic compounds or aromatic compounds containing
hetero atoms may also be separated using the subject invention. The
aromatic compounds may have from one to four or more benzene rings.
Oxygenated aromatics such as ethers, esters and alcohols, and
carbohydrates such as saccharides, organic acids, proteins and
amino acids are other classes of suitable feed compounds. The
subject apparatus and process can be used for the separation of one
specific compound from a mixture or for the separation of a class
of compounds from one or more classes of different compounds.
The subject invention can also be characterized as a simulated
moving bed process for separating a multicomponent feed stream by
liquid chromatography which comprises continuously repeating the
following steps at each of a plurality of serially interconnected
adsorbent chambers used in the process: passing the feed stream,
which comprises an extract component and a raffinate component,
through a first header conduit and into a first multiport valve,
which is associated with the inlet of a first adsorbent chamber,
and then through a first transfer conduit and into the inlet of the
first adsorbent chamber, with the first adsorbent chamber being
maintained at adsorption promoting conditions and containing a bed
of adsorbent which is capable of selectively adsorbing the extract
component; simultaneously passing an internal process stream
removed from the outlet of a second adsorbent chamber, located
immediately upstream of the first adsorbent chamber, through a
second multiport valve, associated with the outlet of second
adsorbent chamber, and into the inlet of the first adsorbent
chamber while removing a first process stream from the outlet of
the first adsorbent chamber and passing the first process stream
through a third multiport valve, associated with the outlet of
first adsorbent chamber, and into the inlet of a third adsorbent
chamber, which is located immediately downstream of the first
adsorbent chamber; indexing the positions of valves present in the
apparatus such that the feed stream is passed into an adsorbent
chamber located downstream of the first adsorbent chamber;
withdrawing an extract stream comprising the extract component from
the outlet of the second adsorbent chamber, passing the extract
stream through the second multiport valve, associated with the
outlet of the second adsorbent chamber, and then dividing the
extract stream into a first portion, which is passed into the first
adsorbent chamber as said internal process stream, and a second
portion which is passed first into the first multiport valve,
associated with the inlet of the first adsorbent chamber, and then
into a second header conduit and removed from the process as an
extract product stream; indexing the positions of valves in the
apparatus used such that the extract stream is withdrawn from an
adsorbent chamber located downstream of the first adsorbent
chamber; passing a mobile phase stream comprising a desorbent
compound through a third header conduit and the fourth multiport
valve and into the first adsorbent chamber, with the effluent of
the first adsorbent chamber being passed into the third adsorbent
chamber through the third multiport valve; indexing the positions
of valves used in the apparatus such that the mobile phase stream
is passed into an adsorbent chamber located downstream of the first
adsorbent chamber; and, withdrawing a raffinate stream from the
outlet of the second adsorbent chamber and passing the extract
stream through the second and fourth multiport valves and into a
fourth header conduit, and withdrawing the raffinate stream from
the process.
* * * * *